Zar H A, Tanigawa K, Kim Y M, Lancaster J R
Safar Center for Resuscitation Research and the Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Anesthesiology. 1999 Apr;90(4):1103-11. doi: 10.1097/00000542-199904000-00025.
Mild hypothermia, a promising therapy being evaluated for various clinical situations, may suppress the formation of reactive oxygen species during reperfusion and may ameliorate microcirculatory perfusion failure (the "no-reflow phenomenon").
Isolated rat livers underwent 30 min of perfusion, 2.5 h of ischemia, and 3 h of reperfusion. The temperature was maintained at 34 degrees C (mild hypothermia, n = 5) or 38 degrees C (normothermia, n = 6) for all three periods by perfusion of a modified Krebs Henseleit solution, air surface cooling, or both. A third group of livers was normothermic before and during ischemia and mildly hypothermic during reperfusion (reperfusion hypothermia, n = 6). Control livers had 3 h of perfusion at normothermia. Chemiluminescence (a measure of the generation of reactive oxygen species) and hepatic vascular resistance were monitored simultaneously to evaluate the effect of temperature on the formation of reactive oxygen species and the development of no reflow. Also measured were thiobarbituric acid reactive species and lactate dehydrogenase, as indicators of oxidative stress and cell injury.
Mild hypothermia decreased formation of reactive oxygen species and postischemic increases in vascular resistance. Reperfusion hypothermia also decreased postischemic increases in vascular resistance, but not as effectively as did mild hypothermia. Levels of thiobarbituric acid reactive species were lower for reperfusion hypothermia than for mild hypothermia at only 0 and 30 min of reperfusion. Lactate dehydrogenase was significant only at 0 min of reperfusion for the normothermic group. Oxygen consumption did not change.
The prevention of hepatic vascular injury by suppression of oxidative stress may be an important protective mechanism of mild hypothermia.
亚低温作为一种正在针对各种临床情况进行评估的有前景的治疗方法，可能会抑制再灌注期间活性氧的形成，并可能改善微循环灌注衰竭（“无复流现象”）。
将离体大鼠肝脏进行30分钟灌注、2.5小时缺血和3小时再灌注。在所有三个阶段，通过灌注改良的克雷布斯-亨塞尔特溶液、空气表面冷却或两者结合，将温度维持在34℃（亚低温，n = 5）或38℃（正常体温，n = 6）。第三组肝脏在缺血前和缺血期间为正常体温，在再灌注期间为亚低温（再灌注亚低温，n = 6）。对照肝脏在正常体温下进行3小时灌注。同时监测化学发光（活性氧生成的一种测量方法）和肝血管阻力，以评估温度对活性氧形成和无复流发展的影响。还测量了硫代巴比妥酸反应性物质和乳酸脱氢酶，作为氧化应激和细胞损伤的指标。
亚低温减少了活性氧的形成以及缺血后血管阻力的增加。再灌注亚低温也减少了缺血后血管阻力的增加，但效果不如亚低温显著。仅在再灌注0分钟和30分钟时，再灌注亚低温组的硫代巴比妥酸反应性物质水平低于亚低温组。乳酸脱氢酶仅在正常体温组再灌注0分钟时显著升高。氧消耗没有变化。
通过抑制氧化应激来预防肝血管损伤可能是亚低温的一种重要保护机制。
